Study Evaluating Rapid Infusion Rituximab in Patients With Autoimmune Diseases

Background Rituximab is a human/murine monoclonal antibody targeted at the CD20 antigen
(cluster of differentiation antigen 20) on B-lymphocytes. The CD20 antigen is expressed in
over 90% of B-cell non-Hodgkin's lymphomas. B cells are also believed to play a role in the
pathogenesis of other oncologic and non-oncologic disorders. Targeting B cells appears to
have a role in decreasing autoimmune and inflammatory processes, as well as antibody
production in many autoimmune diseases. Rituximab is approved for the treatment of
non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA)
in combination with methotrexate, wegener's granulomatosis, and microscopic polyangiitis in
combination with glucocorticoids. Although rituximab is not approved for multiple sclerosis,
myasthenia gravis, or other autoimmune diseases, it is commonly used later in the treatment
course for patients that are not responding to other treatment options. Rituximab's main
limitation is the occurrence of infusion-related reactions (IRR). These reactions can include
fever, chills, rash, respiratory compromise, and a variety of other symptoms, including
death. The incidence of IRR is known to vary depending on the rituximab indication. The
incidence of IRR with the first infusion of rituximab is approximately 77% with NHL, 27% with
RA, and 12% with wegener's granulomatosis and microscopic polyangiitis. The incidence of IRR
decreases with subsequent infusions of rituximab to approximately 5-10%. According to the
National Cancer Institute, there are 5 grades of IRR. In general, grade 1 reactions are
classified as asymptomatic or only mild symptoms that do not require intervention. Grade 2
reactions are classified as moderate with minimal, local, or noninvasive interventions
required. Grade 3 reactions are classified as severe and medically significant, but not
immediately life-threatening. These reactions require hospitalization or prolongation of a
current hospitalization. Grade 4 reactions are classified as life-threatening with urgent
interventions required. Grade 5 reactions are classified as death related to an adverse drug
event. The incidence of IRR is a chief concern for patients, nurses, and other healthcare
providers.

The package labeling recommends the administration of a standard infusion of rituximab for
all patients initiating rituximab therapy to minimize IRR. If this infusion is tolerated then
subsequent infusions may be titrated up to a faster rate to decrease infusion time. Based on
the manufacturer's package insert, rituximab is infused at a rate of 50 mg/hr and can be
increased every 30 minutes by 50 mg/hr (maximum rate of 400 mg/hr). If a grade 3 or 4 IRR
does not occur, subsequent infusions are given at a rate of 100 mg/hr and can be increased
every 30 minutes by 100 mg/hr (maximum rate of 400 mg/hr). The average infusion time is
estimated to be 4-6 hours for the first infusion, and 3-4 hours for subsequent infusions.
Rituximab is typically given in cycles and the timing will vary depending on the indication.

Inclusion Criteria:

- Autoimmune patient at Wake Forest Baptist Health that is eligible for rituximab
therapy

- Tolerate the standard infusion rituximab with ≤ grade 2 hypersensitivity reaction

- Consent to participate in the rapid infusion study

- Age ≥ 18 years ≤ 80 years

Exclusion Criteria:

- Tolerate the standard infusion rituximab with ≥ grade 3 hypersensitivity reaction

- Neurocognitive impairment (i.e. dementia, Alzheimers, et al)